Infectious mononucleosis (IM) is a lymphoproliferative syndrome characterized by an atypical lymphocytosis. Most cases are caused by the Epstein-Barr virus (EBV), however a smaller proportion results from infection with cytomegalovirus (CMV) and mononucleosis can be induced, albeit rarely, by adenovirus, rubella and Toxoplasma gondii. The pathogenesis of the disease caused by EBV has received most study. EBV infects the B cell and the atypical lymphocytes include a large T cell component which is capable of killing lymphoid cell lines (LCL) of B cell-origin. Most LCL contain EBV and evidence has been presented which suggests that the cytotoxicity may be specific for an EBV-associated antigen. However two factors complicate the hypothesis. First, the generation of cytotoxic cells is not confined to EBV-induced disease but also occurs in mononucleosis caused by CMV; second, even in EBV-IM there is cytotoxicity for EBV-negative LCL which is associated with atypical blast cells. We propose to examine the conditions and kinetics of induction of atypical cells in vitro by EBV antigens or by EBV in association with the B cell. The functional capacities of the cells will be assessed with particular reference to their cytotoxic and regulatory functions and will be compared with those of similar cells induced in vitro by CMV antigens or in vivo in patients with IM. The ultimate objectives of the proposal are to determine whether the atypical cells is a common link between IM induced by various agents, why it is particularly prone to induction by EBV and whether this may have general implication for the control of proliferative disease.